Cholesterol-Enhanced Polylactide-Based Stereocomplex Micelle for Effective Delivery of Doxorubicin

Abstract

Nanoscale micelles as an effective drug delivery system have attracted increasing interest in malignancy therapy. The present study reported the construction of the cholesterol-enhanced doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (CDM/DOX), poly(L-lactide)-based micelle (CLM/DOX), and stereocomplex micelle (CSCM/DOX) from the equimolar enantiomeric 4-armed poly(ethylene glycol)–polylactide copolymers in aqueous condition. Compared with CDM/DOX and CLM/DOX, CSCM/DOX showed the smallest hydrodynamic size of 96 ± 4.8 nm and the slowest DOX release. The DOX-loaded micelles exhibited a weaker DOX fluorescence inside mouse renal carcinoma cells (i.e., RenCa cells) compared to free DOX·HCl, probably because of a slower DOX release. More importantly, all the DOX-loaded micelles, especially CSCM/DOX, exhibited the excellent antiproliferative efficacy that was equal to or even better than free DOX·HCl toward RenCa cells attributed to their successful internalization. Furthermore, all of the DOX-loaded micelles exhibited the satisfactory hemocompatibility compared to free DOX·HCl, indicating the great potential for systemic chemotherapy through intravenous injection.

Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model

“…Apparently, the appropriate size is conducive to the selective accumulation of NG/DOX in the tumor site through the EPR effect. 24,25 In vivo biocompatibility and distribution…”

Epirubicin-Complexed Polypeptide Micelle Effectively and Safely Treats Hepatocellular Carcinoma

“…The IC 50 values of mPEG-b-PGA/EPI at 24 and 48 h were 2.3 and 0.3 µg¨mL´1, respectively, which were significantly higher than those of free EPI at 1.5 and 0.2 µg¨mL´1 (p < 0.01), respectively, whereas the difference of IC 50 values between mPEG-b-PGA/EPI and free EPI was not significant at 72 h, which might be caused by the sustained drug release from the micelle and increased intracellular drug accumulation with time. The excellent blood compatibility of drug-loaded nanoparticles is an important premise for their clinical applications, because most of them will be administrated through intravenous injection [31]. Several studies have verified that the polypeptide-based block copolymer can improve the blood compatibility of free drugs [32,33].…”

“…The excellent blood compatibility of drug-loaded nanoparticles is an important premise for their clinical applications, because most of them will be administrated through intravenous injection [31]. Several studies have verified that the polypeptide-based block copolymer can improve the blood compatibility of free drugs [32,33].…”

PEGylated Polylactide Micelles for Controlled Drug Delivery

“…PEG−PLA micelles has been widely researched and applied as promising nanocarriers for controlled drug delivery [2,9,13]. Most encouragingly, Genexol  -PM, a paclitaxel (PTX)-loaded PEG−PDLLA micelle, is the only clinically approved nanoscale polymer chemotherapeutic up to now, which was exploited by Samyang Genex Co. (Seoul, Korea) [14,15].…”

“…As depicted in Figure 2, several PLA SCMs have been developed tocontrollably deliver different antitumor drugs, such as doxorubicin (DOX) and 10-hydroxycamptothecin (HCPT), in our research group [2,9,10,13]. As a typical example, the DOX-loaded PLLA-based micelle (PLM/DOX), PDLA-based micelle (PDM/DOX), and SCM (SCM/DOX) were fabricated [9].…”